The incorporated parent patent application discloses a single pot process for the preparation of metal picolinates.
In 1996, according to WHO and the International Diabetes Federation, there were 132 million diabetic patients worldwide. This number is expected to increase to 240 millions by 2010. Diabetes is a serious disease that we need to cure.
Trivalent chromium in a trace amounts, is needed by for the metabolism of sugar, protein and fat in the human body. A deficiency of this trace element causes diabetes. Trivalent chromium is distributed in many tissues in human body, with liver and kidney containing the highest amount.
According to a report published in the National Academy of Sciences, in 1980, at page 160, only 0.5% of ingested inorganic chromium is assimilated into the body. Also only 1-2% of most ingested organic chromium compounds is assimilated into the body. In marked contrast to this, the synthetic coordination complex of picolinic acid with chromium is directly available for absorption without competition from other metals as reported in U.S. reissue Pat. No. Re 33988. Published U.S. Patent Application No. 2002 098247 and published PCT application WO 02/36202 disclose that chromium nicotinate composition is used to improve insulin sensitivity, reduces hyperglycemia and reduces hypercholesterolemia.
U.S. Pat. Nos. 6,379,693 and 6,203,819 reveal that chromium nicotinate can be administered as a dietary supplement to the patients for curing diabetes. According to U.S. Pat. No. 5,194,615 it can also be used as Glucose Tolerance Factor (GTF) treatment material. Chromium nicotinate is also reported to be useful as a feed supplement to cattle to improve their milk production (U.S. Pat. No. 6,139,881).
Zinc, a trace element in the human body, is known to participate in the development of sexual organs, promotion of wound healing, activating the immune system and to be a component of a metalloenzyme, which is an accelerator for dehydrogenase. Conventionally zinc oxide formulations have been topically used as medicines for treating skin diseases such as dermatitis, sunburn, neurodermatitis and eczema. These formulations have local astringent action and irritation, and are not usually administered internally. U.S. Pat. Nos. 5,582,817 and 5,696,169 reported that zinc nicotinate can be used in cosmetics and as a drug for ameliorating sunburn and skin diseases, preventing sunburn, relieving irradiation disorders, etc.
In the prior art of preparation of chromium nicotinate, U.S. Pat. Nos. 5,194,615 and 4,923,855 suggested the reaction of an alkali metal salt of nicotinic acid with a trivalent chromium salt. After the completion of reaction, the precipitated chromium complex is filtered and dried.
Further U.S. Pat. Nos. 5,696,169 and 5,582,817 discloses the preparation of zinc nicotinate complex by reacting nicotinic acid with zinc acetate dihydrate, and adjusting the pH to 8.5. However these patents use nicotinic acid and chromium (III) chloride hexahydrate or zinc acetate dihydrate as the starting material for the manufacturer of chromium nicotinate or zinc nicotinate, respectively.
Alkylpyridines can be oxidised by chemical agents such as KMnO4 but these reagents are expensive and can lead to excessive oxidation and thereby cause ring degradation [J. Org. Chem. 14, 14 (1949); J. Chem. Soc. 934 (1946)] and generates allot of MnO2 as solid waste, which has its own problems in disposal. Other methodologies include nitric acid oxidation, which has been reported as a more economical route, but it requires elevated temperature and pressure [Bengtsson, Acta. Chem. Scand.; 9, 832 (1955)]. These harsh conditions cause decarboxylation and thus resulting yield loss of pyridine carboxylic acid. U.S. Pat. No. 2,437,938 reports catalytic air oxidation, but doesn't appear to have general application.
U.S. Pat. No. 2,522,163 relates to preparation of pyridine carboxylic acids from sulfates of alkyl pyridine, quinoline, isoquinolines and alkyl quinolines. That invention is illustrated by an example wherein the preparation of nicotinic acid from beta picoline (3-picoline) is described.
U.S. Pat. No. 2,513,099 discloses a process for oxidising N-heterocyclic compounds containing a pyridine nucleus and an oxidizable organic group attached to the nitrogen containing aromatic nucleus by at least one carbon to carbon linkage. The process involves oxidation by reacting nitric acid with a solution containing the N-heterocyclic compound and a mixture of mercury and copper compounds dissolved in sulphuric acid. This process of oxidation may normally lead to the contamination of the nicotinic acid with undesired metals. While the prior art techniques for preparing chromium nicotinate and zinc nicotinate have been reasonably successful, the presently known and used preparation is rather complex. These techniques involve multi-steps, which makes the product expensive.